Ion channels transduce changes in the extracellular environment into neural activity. The Degenerin/Epithelial sodium channel family of ion channels participates in fundamental processes in many organisms, from salt exchange in mammalian kidneys, mechanotransduction in C. elegans, and peptide sensing in snails. In Drosophila, there are 29 members of this gene family called pickpocket genes (ppk). The molecular, genetic, functional and behavioral assays available in Drosophila provide the opportunity to dissect the function of uncharacterized members of this gene family. In preliminary studies, two members of the ppk gene family have been identified that are exclusively expressed in sensory neurons in the adult Drosophila. The aim of this application is to elucidate their function. The experiments proposed will examine the ligands that are detected by ppk-containing cells, the cellular and behavioral phenotypes associated with loss of specific ppk genes, and response profiles of cells engineered to mis-express ppk ion channels. The proposed experiments will examine the hypothesis that ppk ion channels directly detect extracellular sensory cues. These studies will elucidate the biological role of ppk ion channels and determine the ligands that activate them. Because members of this ion channel family are associated with diverse human diseases, studies of ppk function are directly relevant to human health. PUBLIC HEALTH RELEVANCE: This research is relevant to public health because it examines the function of ion channels that are associated with human disease. Primary malfunctions in these channels underlie the pathophysiology of several important human diseases such as salt-sensitive hypertension and pseudohypoaldosteronism type I, and defects in these channels have been associated with cystic fibrosis and epilepsy. A basic understanding of the ligands that gate these ion channels may ultimately provide insight into human disease genes, with a direct impact on public health.